Aminoglycoside dosing has been studied in the obese population, typically recommending an adjusted weight utilizing a 40% dosing weight correction factor (IBW + 0.4 × (TBW–IBW)). These studies included limited numbers of morbidly obese patients and were not done in the era of extended interval aminoglycoside dosing. Here, we report a retrospective evaluation of morbidly obese patients receiving gentamicin or tobramycin at our hospital. The objective of this study was to evaluate the accuracy of the commonly recommended adjusted weight for weight-based dosing. There were 31 morbidly obese patients who received gentamicin or tobramycin 5–7？mg/kg every 24 hours using a 40% dosing weight correction factor. Our institution utilizes 16-hour postdose concentrations to monitor extended interval aminoglycosides. Twenty-two of the 31 patients (71%) achieved an appropriate serum drug concentration. Four patients (13%) were found to be supratherapeutic and 5 patients (16%) subtherapeutic. The only variable that correlated with supratherapeutic levels was older age ( ). Our study helps to validate the current dosing weight correction factor (40%) in the morbidly obese population. We recommend caution when dosing aminoglycosides in morbidly obese patients who are of older age. 1. Background The World Health Organization (WHO) estimated that 500 million people worldwide were obese in 2008 and that number would increase to 700 million by 2015 [1]. In 2011, all 50 states in the United States estimated that 20% or more of their adult population was obese (body mass index ≥ 30？kg/m2); 12 out of the 50 states estimated that more than 30% of their adult population was in this category [2]. Not only the prevalence of obesity is rapidly increasing, but the weight of obese patients continues to rise with five percent of Americans now being considered morbidly obese (body mass index ≥ 40？kg/m2) [3]. Several clinical studies, case reports, and review articles have described that pharmacokinetic properties are altered in obese patients compared to ideal body weight (IBW) patients [4–15]. There are four main issues that merit discussion when evaluating pharmacokinetic alterations in obesity: absorption, distribution, metabolism, and elimination. The absorption of most drugs is thought to be relatively unaffected by obesity [16]. However, studies in obese patients have shown an altered volume of distribution due to their increased blood flow and cardiac output, changes in protein binding, and organ mass [16, 17]. The metabolism of drugs in this particular population is poorly
References
[1]
The World Health Organization, “Obesity Fact Sheet,” March 2013, http://www.who.int/topics/obesity/en/.
[2]
Centers for Disease Control and Prevention, “Adult Obesity Facts,” March 2013, http://www.cdc.gov/obesity/data/adult.html.
[3]
M. P. Pai and D. T. Bearden, “Antimicrobial dosing considerations in obese adult patients: insights from the society of infectious diseases pharmacists,” Pharmacotherapy, vol. 27, no. 8, pp. 1081–1091, 2007.
[4]
D. Newman, M. H. Scheetz, O. A. Adeyemi et al., “Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual,” Annals of Pharmacotherapy, vol. 41, no. 10, pp. 1734–1739, 2007.
[5]
J. B. Lee, S. Winstead, and A. M. Cook, “Pharmacokinetic alterations in obesity,” Orthopedics, vol. 29, no. 11, pp. 984–988, 2006.
[6]
G. Cheymol, “Clinical pharmacokinetics of drugs in obesity—an update,” Clinical Pharmacokinetics, vol. 25, no. 2, pp. 103–114, 1993.
[7]
S. Viriyayudhakorn, S. Thitiarchakul, S. Nachaisit, P. C. Ho, and S. Wanwimolruk, “Pharmacokinetics of quinine in obesity,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 94, no. 4, pp. 425–428, 2000.
[8]
G. Cheymol, “Effects of obesity on pharmacokinetics: implications for drug therapy,” Clinical Pharmacokinetics, vol. 39, no. 3, pp. 215–231, 2000.
[9]
M. J. Lind, J. M. Margison, T. Cerny, N. Thatcher, and P. M. Wilkinson, “Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution,” Cancer Chemotherapy and Pharmacology, vol. 25, no. 2, pp. 139–142, 1989.
[10]
S. Lotia and M. C. Bellamy, “Anaesthesia and morbid obesity,” Continuing Education in Anaesthesia, Critical Care and Pain, vol. 8, no. 5, pp. 151–156, 2008.
[11]
R. A. Blouin, L. A. Bauer, and D. D. Miller, “Vancomycin pharmacokinetics in normal and morbidly obese subjects,” Antimicrobial Agents and Chemotherapy, vol. 21, no. 4, pp. 575–580, 1982.
[12]
I. Sketris, T. Lesar, D. E. Zaske, and R. J. Cipolle, “Effect of obesity on gentamicin pharmacokinetics,” Journal of Clinical Pharmacology, vol. 21, no. 7, pp. 288–293, 1981.
[13]
D. T. Bearden and K. A. Rodvold, “Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics,” Clinical Pharmacokinetics, vol. 38, no. 5, pp. 415–426, 2000.
[14]
B. L. Erstad, “Dosing of medications in morbidly obese patients in the intensive care unit setting,” Intensive Care Medicine, vol. 30, no. 1, pp. 18–32, 2004.
[15]
S. N. Schwartz, G. J. Pazin, and J. A. Lyon, “A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects,” Journal of Infectious Diseases, vol. 138, no. 4, pp. 499–505, 1978.
[16]
R. A. Blouin and G. W. Warren, “Pharmacokinetic considerations in obesity,” Journal of Pharmaceutical Sciences, vol. 88, no. 1, pp. 1–7, 1999.
[17]
R. Wurtz, G. Itokazu, and K. Rodvold, “Antimicrobial dosing in obese patients,” Clinical Infectious Diseases, vol. 25, no. 1, pp. 112–118, 1997.
[18]
D. J. Rea, J. K. Heimbach, J. P. Grande et al., “Glomerular volume and renal histology in obese and non-obese living kidney donors,” Kidney International, vol. 70, no. 9, pp. 1636–1641, 2006.
[19]
R. J. Bosma, J. A. Krikken, J. J. Homan van der Heide, P. E. De Jong, and G. J. Navis, “Obesity and renal hemodynamics,” Contributions to Nephrology, vol. 151, pp. 184–202, 2006.
[20]
L. A. Bauer, W. A. Drew Edwards, E. Patchen Dellinger, and D. A. Simonowitz, “Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients,” European Journal of Clinical Pharmacology, vol. 24, no. 5, pp. 643–647, 1983.
[21]
A. M. Traynor, A. N. Nafziger, and J. S. Bertino Jr., “Aminoglycoside dosing weight correction factors for patients of various body sizes,” Antimicrobial Agents and Chemotherapy, vol. 39, no. 2, pp. 545–548, 1995.
[22]
M. P. Pai, A. N. Nafziger, and J. S. Bertino Jr., “Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients,” Antimicrobial Agents and Chemotherapy, vol. 55, no. 9, pp. 4006–4011, 2011.
[23]
F. Vincent, N. El-Khoury, E. Rondeau, and A. A. El Solh, “Renal function in critically ill, morbidly obese patients,” American Journal of Respiratory and Critical Care Medicine, vol. 169, no. 12, pp. 1332–1333, 2004.
[24]
S. A. Spinler, “Predictive performance of ten equations for estimating creatinine clearance in cardiac patients,” Annals of Pharmacotherapy, vol. 32, no. 12, pp. 1275–1283, 1998.
[25]
D. E. Salazar and G. B. Corcoran, “Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass,” American Journal of Medicine, vol. 84, no. 6, pp. 1053–1060, 1988.
[26]
R. E. Dionne, L. A. Bauer, G. A. Gibson, W. O. Griffen Jr., and R. A. Blouin, “Estimating creatinine clearance in morbidity obese patients,” American Journal of Hospital Pharmacy, vol. 38, no. 6, pp. 841–844, 1981.
[27]
D. P. Nicolau, C. D. Freeman, P. P. Belliveau, C. H. Nightingale, J. W. Ross, and R. Quintiliani, “Experience with a once-daily aminoglycoside program administered to 2,184 adult patients,” Antimicrobial Agents and Chemotherapy, vol. 39, no. 3, pp. 650–655, 1995.
[28]
D. N. Gilbert, B. L. Lee, R. J. Dworkin et al., “A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate,” American Journal of Medicine, vol. 105, no. 3, pp. 182–191, 1998.
